Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. The majority of this morbidity and mortality is concentrated in infants delivered prior to 30 weeks' gestational age. One of the best predictors of poor outcome in the current pregnancy is a history of poor outcome in a previous pregnancy. Recent data from the University of Alabama at Birmingham (UAB) indicate that over one half of women who have a spontaneous pregnancy loss between 19 and 24 weeks' gestation in an index pregnancy have another preterm birth in the subsequent pregnancy. Data from several institutions including UAB support the hypothesis that upper genital tract colonization with Ureaplasma urealyticum (U. urealyticum) and other microorganisms may have an important etiologic role in spontaneous preterm birth. Although numerous microorganisms have been isolated, U. urealyticum has consistently been found to be the predominant microorganism isolated from both the chorioamnion and the amniotic fluid in women with spontaneous preterm labor. Data indicate that the association between upper tract microbial colonization and spontaneous preterm birth is inversely proportional to gestational age, i.e., the earlier the gestational age of a preterm birth due to spontaneous preterm labor, the stronger the association with microbial invasion of the upper genital tract. Also, colonization of the endometrium with U. urealyticum and histologic evidence of inflammation have been demonstrated in non-pregnant women. To date, the role of microbial invasion of the upper genital tract in spontaneous second trimester pregnancy losses is much less well studied. This investigation is designed to provide a systematic microbiologic evaluation of the upper genital tract in women with a spontaneous second trimester pregnancy loss or early preterm birth, not only at the time of the spontaneous loss, but also during the interval between pregnancies. Particular emphasis will be placed on the role of U. urealyticum; however, other potential pathogens including aerobic and anaerobic bacteria will also be investigated. Hypotheses to be tested include: l) Upper genital tract colonization with U. urealyticum and other microorganisms is associated with early spontaneous pregnancy losses and 2) Chronic colonization of the endometrium with U. urealyticum and other microorganisms during the interval between pregnancies may partially explain the high incidence of spontaneous preterm birth in women with a previous spontaneous second trimester loss. Accomplishment of the proposed specific aim will also significantly complement the other projects in achieving the overall goal of the multidisciplinary proposal to prevent and confine sexually transmitted disease related morbidity.